VEMP_SARS2
ID VEMP_SARS2 Reviewed; 75 AA.
AC P0DTC4;
DT 22-APR-2020, integrated into UniProtKB/Swiss-Prot.
DT 22-APR-2020, sequence version 1.
DT 03-AUG-2022, entry version 12.
DE RecName: Full=Envelope small membrane protein {ECO:0000255|HAMAP-Rule:MF_04204};
DE Short=E;
DE Short=sM protein {ECO:0000255|HAMAP-Rule:MF_04204};
GN Name=E {ECO:0000255|HAMAP-Rule:MF_04204}; ORFNames=4;
OS Severe acute respiratory syndrome coronavirus 2 (2019-nCoV) (SARS-CoV-2).
OC Viruses; Riboviria; Orthornavirae; Pisuviricota; Pisoniviricetes;
OC Nidovirales; Cornidovirineae; Coronaviridae; Orthocoronavirinae;
OC Betacoronavirus; Sarbecovirus.
OX NCBI_TaxID=2697049;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=32015508; DOI=10.1038/s41586-020-2008-3;
RA Wu F., Zhao S., Yu B., Chen Y.-M., Wang W., Song Z.-G., Hu Y., Tao Z.-W.,
RA Tian J.-H., Pei Y.-Y., Yuan M.-L., Zhang Y.-L., Dai F.-H., Liu Y.,
RA Wang Q.-M., Zheng J.-J., Xu L., Holmes E.C., Zhang Y.-Z.;
RT "A new coronavirus associated with human respiratory disease in China.";
RL Nature 579:265-269(2020).
RN [2]
RP FUNCTION, AND INTERACTION WITH HUMAN MPP5.
RX PubMed=32891874; DOI=10.1016/j.micinf.2020.08.006;
RA De Maio F., Lo Cascio E., Babini G., Sali M., Della Longa S., Tilocca B.,
RA Roncada P., Arcovito A., Sanguinetti M., Scambia G., Urbani A.;
RT "Improved binding of SARS-CoV-2 Envelope protein to tight junction-
RT associated PALS1 could play a key role in COVID-19 pathogenesis.";
RL Microbes Infect. 22:592-597(2020).
RN [3]
RP TOPOLOGY.
RX PubMed=32898469; DOI=10.1098/rsob.200209;
RA Duart G., Garcia-Murria M.J., Grau B., Acosta-Caceres J.M.,
RA Martinez-Gil L., Mingarro I.;
RT "SARS-CoV-2 envelope protein topology in eukaryotic membranes.";
RL Open Biol. 10:200209-200209(2020).
RN [4]
RP STRUCTURE BY NMR OF 8-38, SUBUNIT, SUBCELLULAR LOCATION, AND TOPOLOGY.
RX PubMed=33177698; DOI=10.1038/s41594-020-00536-8;
RA Mandala V.S., McKay M.J., Shcherbakov A.A., Dregni A.J., Kolocouris A.,
RA Hong M.;
RT "Structure and drug binding of the SARS-CoV-2 envelope protein
RT transmembrane domain in lipid bilayers.";
RL Nat. Struct. Mol. Biol. 27:1202-1208(2020).
RN [5]
RP FUNCTION.
RX PubMed=33229438; DOI=10.1074/jbc.ra120.016175;
RA Boson B., Legros V., Zhou B., Siret E., Mathieu C., Cosset F.L.,
RA Lavillette D., Denolly S.;
RT "The SARS-CoV-2 Envelope and Membrane proteins modulate maturation and
RT retention of the Spike protein, allowing assembly of virus-like
RT particles.";
RL J. Biol. Chem. 296:100111-100111(2020).
CC -!- FUNCTION: Plays a central role in virus morphogenesis and assembly.
CC Acts as a viroporin and self-assembles in host membranes forming
CC pentameric protein-lipid pores that allow ion transport. Also plays a
CC role in the induction of apoptosis (By similarity). Regulates the
CC localization of S protein at cis-Golgi, the place of virus budding
CC (PubMed:33229438). May act by slowing down the cell secretory pathway
CC (PubMed:33229438). May interfere with tight-junction stability by
CC interacting with host MPP5. This would result in disruption of
CC epithelial barriers, thereby amplifying inflammatory processes
CC (PubMed:32891874). {ECO:0000255|HAMAP-Rule:MF_04204,
CC ECO:0000269|PubMed:33229438, ECO:0000303|PubMed:32891874}.
CC -!- SUBUNIT: Homopentamer (PubMed:33177698). Interacts with membrane
CC protein M in the budding compartment of the host cell, which is located
CC between endoplasmic reticulum and the Golgi complex. Interacts with
CC Nucleoprotein (By similarity). Interacts with the accessory proteins 3a
CC and 7a (By similarity). Interacts (via C-terminus) with human MPP5 (via
CC PDZ domain); this inhibits the interaction between human MPP5 and human
CC CRB3, and causes disruption of epithelial cells tight junctions
CC (PubMed:32891874). {ECO:0000250|UniProtKB:P59637, ECO:0000255|HAMAP-
CC Rule:MF_04204, ECO:0000269|PubMed:33177698,
CC ECO:0000303|PubMed:32891874}.
CC -!- INTERACTION:
CC P0DTC4; P0DTC4: E; NbExp=3; IntAct=EBI-25475850, EBI-25475850;
CC P0DTC4; P0DTC9: N; NbExp=3; IntAct=EBI-25475850, EBI-25475856;
CC P0DTC4; O95429: BAG4; Xeno; NbExp=3; IntAct=EBI-25475850, EBI-2949658;
CC P0DTC4; PRO_0000018590 [Q07021]: C1QBP; Xeno; NbExp=3; IntAct=EBI-25475850, EBI-14032968;
CC P0DTC4; Q8N3R9: PALS1; Xeno; NbExp=6; IntAct=EBI-25475850, EBI-2513978;
CC P0DTC4; O75360: PROP1; Xeno; NbExp=3; IntAct=EBI-25475850, EBI-9027467;
CC P0DTC4; P61165: TMEM258; Xeno; NbExp=3; IntAct=EBI-25475850, EBI-12019210;
CC -!- SUBCELLULAR LOCATION: Host Golgi apparatus membrane {ECO:0000255|HAMAP-
CC Rule:MF_04204}; Single-pass type III membrane protein
CC {ECO:0000255|HAMAP-Rule:MF_04204, ECO:0000269|PubMed:32898469,
CC ECO:0000269|PubMed:33177698}. Note=The cytoplasmic tail functions as a
CC Golgi complex-targeting signal. {ECO:0000255|HAMAP-Rule:MF_04204}.
CC -!- POLYMORPHISM: Variant Omicron/BA.1 and BA.2 belong to a lineage first
CC isolated in South Africa (November 2021). {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the betacoronaviruses E protein family.
CC {ECO:0000255|HAMAP-Rule:MF_04204}.
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DR EMBL; MN908947; QHD43418.1; -; Genomic_RNA.
DR RefSeq; YP_009724392.1; NC_045512.2.
DR PDB; 7K3G; NMR; -; A/B/C/D/E=8-38.
DR PDB; 7M4R; EM; 3.65 A; C=58-75.
DR PDB; 7NTK; X-ray; 1.90 A; C/E/G/H=68-75.
DR PDBsum; 7K3G; -.
DR PDBsum; 7M4R; -.
DR PDBsum; 7NTK; -.
DR BMRB; P0DTC4; -.
DR SMR; P0DTC4; -.
DR BioGRID; 4383845; 1040.
DR IntAct; P0DTC4; 51.
DR TCDB; 1.A.65.1.7; the coronavirus viroporin e protein (viroporin e) family.
DR ABCD; P0DTC4; 9 sequenced antibodies.
DR GeneID; 43740570; -.
DR KEGG; vg:43740570; -.
DR Reactome; R-HSA-191650; Regulation of gap junction activity.
DR Reactome; R-HSA-420029; Tight junction interactions.
DR Reactome; R-HSA-9694322; Virion Assembly and Release.
DR Reactome; R-HSA-9694493; Maturation of protein E.
DR Reactome; R-HSA-9694614; Attachment and Entry.
DR Reactome; R-HSA-9694635; Translation of Structural Proteins.
DR Reactome; R-HSA-9705671; SARS-CoV-2 activates/modulates innate and adaptive immune responses.
DR Reactome; R-HSA-9705677; SARS-CoV-2 targets PDZ proteins in cell-cell junction.
DR PRO; PR:P0DTC4; -.
DR Proteomes; UP000464024; Genome.
DR GO; GO:0044178; C:host cell Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-UniRule.
DR GO; GO:0055036; C:virion membrane; TAS:Reactome.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0044662; P:disruption by virus of host cell membrane; IEA:UniProtKB-UniRule.
DR GO; GO:0039707; P:pore formation by virus in membrane of host cell; IEA:InterPro.
DR GO; GO:0046760; P:viral budding from Golgi membrane; IEA:UniProtKB-UniRule.
DR CDD; cd21536; SARS-CoV-2_E; 1.
DR HAMAP; MF_04204; BETA_CORONA_E; 1.
DR InterPro; IPR043506; E_protein_bCoV.
DR InterPro; IPR003873; E_protein_CoV.
DR InterPro; IPR044377; E_SARS-CoV-2.
DR Pfam; PF02723; CoV_E; 1.
DR PROSITE; PS51926; COV_E; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Apoptosis; Host Golgi apparatus; Host membrane; Membrane;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..75
FT /note="Envelope small membrane protein"
FT /id="PRO_0000449651"
FT TOPO_DOM 1..13
FT /note="Virion surface"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04204,
FT ECO:0000305|PubMed:32898469"
FT TRANSMEM 14..34
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04204,
FT ECO:0000269|PubMed:33177698, ECO:0000305|PubMed:32898469"
FT TOPO_DOM 35..75
FT /note="Intravirion"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04204,
FT ECO:0000305|PubMed:32898469"
FT MOTIF 72..75
FT /note="PDZ-binding; required for interaction with human
FT MPP5"
FT /evidence="ECO:0000250|UniProtKB:P59637"
FT VARIANT 9
FT /note="T -> I (in strain: Omicron/BA.1, Omicron/BA.2,
FT Omicron/BA.2.12.1, Omicron/BA.4, Omicron/BA.5)"
FT /evidence="ECO:0000305"
FT VARIANT 21
FT /note="L -> F (in strain: Eta/B.1.525)"
FT /evidence="ECO:0000305"
FT VARIANT 71
FT /note="P -> L (in strain: Beta/B.1.351)"
FT /evidence="ECO:0000305"
FT HELIX 11..18
FT /evidence="ECO:0007829|PDB:7K3G"
FT HELIX 19..21
FT /evidence="ECO:0007829|PDB:7K3G"
FT HELIX 22..36
FT /evidence="ECO:0007829|PDB:7K3G"
SQ SEQUENCE 75 AA; 8365 MW; 5C431BD2AA1B6B99 CRC64;
MYSFVSEETG TLIVNSVLLF LAFVVFLLVT LAILTALRLC AYCCNIVNVS LVKPSFYVYS
RVKNLNSSRV PDLLV
